The long-term objectives of the Epidemiology Project are to more fully establish the epidemiology of Rett syndrome and provide future direction for the primary and secondary prevention of this devastating neurologic disorder. These accomplishments will be met through the results of several interdependent studies based on sound epidemiologic methods. the first is the population-based Rett syndrome registries and derivative pilot case-control study. The second is the collaborative, full-scale survival study and the derivative National Rett Syndrome Data Bank and electronic network. Specific aims for the registries include 1) maintaining the population- based Texas Rett Syndrome Registry to provide a more complete, stable estimate of the prevalence of Rett syndrome, test the hypothesis that Rett syndrome does not differentially occur by race/ethnicity, investigate the stability of yearly prevalences from 1988 to 1998, investigate seasonal variation of the occurrence of Rett syndrome, and 2) expanding the registry to the population-based Oregon Rett syndrome Registry to validate the methodology of the registry and, determine if the prevalences of Rett syndrome differ by U.S. populations. Specific aims of the pilot case-control study include developing and thoroughly testing for reliability and validity a questionnaire to include epidemiologic variables necessary to identify trends for specific, potential risk factors for Rett syndrome. Specific aims for the survival study include 1) continuing follow-up of the population-based cohorts of the registry, 2) continuing collaboration with the International Rett Syndrome Association to enlarge the survival and prognostic study data base, 3) establishing a network of child neurologist-collaborators who will assist with the assembly of large, well characterized and representative cohort of Rett patients, and 4) following all three cohorts to determine all-cause and cause-specific mortality rates, risk factors for death and specific causes of death in Rett syndrome and predictors of a more favorable course of Rett syndrome. The specific aim of the National Rett syndrome Data Bank and electronic network is to provide a basis for scientific communication and collaboration among interested and experienced investigators throughout the U.S. regarding future epidemiologic and longitudinal investigations, drug or intervention trials and etiopathogenetic studies. The Epidemiology Project will employ a prospective cohort design for the registries and survival studies and a retrospective design for the pilot case-control study. Demographic and clinical data will be maintained with state of the art computer facilities thus maximizing validity and data integrity. Prevalence will be estimated and survival analyses will be conducted to identify determinants of occurrence and prognosis. Preliminary case-control analyses will explore prevailing causal hypotheses and suggest new directions for future genetic and epidemiologic studies.